Tag: pubmed

JAMA Netw Open. 2025 May 1;8(5):e258330. doi: 10.1001/jamanetworkopen.2025.8330.

ABSTRACT

IMPORTANCE: Treatments are urgently needed for the more than 9500 rare diseases with no US Food and Drug Administration-approved therapies. Although repurposing can be less time- and cost-intensive compared with novel drug development, hurdles have impeded systematic repurposing. Rare disease nonprofit organizations (RDNPs) are well-positioned to overcome barriers and have spearheaded rare disease repurposing efforts for decades. However, no comprehensive data are available on the state of rare disease repurposing or features of successful efforts.

OBJECTIVE: To characterize the state of rare disease drug repurposing, identify factors associated with successful outcomes, and share thematic insights using the interactive Repurposing of All Drugs, Mapping All Paths (ROADMAP) Project web tool.

DESIGN, SETTING, AND PARTICIPANTS: The ROADMAP study was a qualitative study using a mixed-methods analysis of US-based RDNP leaders and their stakeholders, including a national survey and semistructured interviews of RDNP leaders, conducted from September 29, 2021, to January 6, 2022. Surveys and interviews revealed themes associated with RDNP strategies, timelines, and support mechanisms. Data were analyzed from January 22, 2024, to April 23, 2024.

MAIN OUTCOMES AND MEASURES: The primary survey outcome was the repurposing project stage (abandoned, early, clinical, late, or successful). Qualitative outcomes included themes characterizing repurposing experiences. Two random forest models of drug- and disease- specific as well as organization-specific variables were used to evaluate factor importance toward inferring the project stage. Orthogonal significance testing was conducted using Spearman rank correlation, and P values in each model were corrected for multiple hypothesis testing using a Benjamini-Hochberg procedure.

RESULTS: Representative organizations submitted survey responses, including 147 of 698 potential US-based RDNPs. The median RDNP age was 10 years (IQR, 5-20 years), and the median annual revenue was $355 390 (IQR, $90 028-$946 108). Among 34 leaders who were interviewed, representing 25 RDNPs, 23 were female (67.6%), and the RDNPs had a median age of 15 years (IQR, 6-19 years) and a median revenue of $670 719 (IQR, $193 587-$1 830 890). Among the surveyed RDNPs, 58 of 138 (42.0%) specifically identifying their involvement in repurposing supported repurposing projects, and 94 drugs were in various stages of repurposing, of which 23 met success criteria (5 with US Food and Drug Administration approval and 18 with off-label use with subjective benefit). Survey factors associated with successful outcomes included nonprofit-supported patient recruitment into trials (Gini importance, 3.90; ρ = 0.50; adjusted P < .001) and provision of nonfinancial research support (Gini importance, 0.69; ρ = 0.33; adjusted P = .02). Interview themes were synthesized into a 5-stage repurposing framework with roadblocks and recommendations that included (1) enabling drug repurposing, (2) identifying a drug therapy, (3) validating a drug therapy, (4) clinical use and testing, and (5) reaching an optimal end point for clinical practice.

CONCLUSIONS AND RELEVANCE: The findings of this qualitative study of RDNP repurposing suggest that several opportunities were associated with successful outcomes and can be considered to optimize systematic repurposing among RDNPs, external collaborators, and policymakers with the use of an interactive tool showcasing insights to facilitate data-driven drug repurposing.

PMID:40323602 | DOI:10.1001/jamanetworkopen.2025.8330

JAMA Netw Open. 2025 May 1;8(5):e258353. doi: 10.1001/jamanetworkopen.2025.8353.

ABSTRACT

IMPORTANCE: Patients with cancer and cancer survivors frequently experience symptoms that increase the need for health care services and impair quality of life. Effective symptom management is critical for comprehensive patient-centered cancer care.

OBJECTIVE: To evaluate the effectiveness of adding a bilingual (English and Spanish), web-based self-management program to an electronic health record (EHR)-integrated patient-reported outcome for cancer (cPRO) assessment in reducing symptom burden and health care resource use (HCRU).

DESIGN, SETTING, AND PARTICIPANTS: This patient-level randomized clinical trial was performed at the Northwestern Memorial HealthCare system in Chicago, Illinois. Participants included 1614 adult patients with cancer or cancer survivors in 30 clinics who were enrolled between April 1, 2020, and April 8, 2023, and followed up for 12 months until May 8, 2024.

INTERVENTIONS: Usual care (UC) consisting of an EHR-integrated cPRO assessment or enhanced care (EC), which offered an additional tailored web-based self-management program.

MAIN OUTCOMES AND MEASURES: Patient-Reported Outcomes Measurement Information System measures of anxiety, depression, fatigue, pain interference, and physical function collected at baseline and monthly for 12 months. Secondary outcomes included HCRU measures (inpatient and/or observation visits and days, emergency department and/or urgent care visits, and days of hospital stay).

RESULTS: A total of 1614 patients were included in the analysis, with 804 randomized to EC and 810 to UC. The mean (SD) age was 61 (13) years; 1095 patients (67.8%) were female. Only 419 EC participants (52.1%) accessed the website, with only 197 (47%) returning; the median time per visit was 45 seconds (IQR, 45-105 seconds). There were no statistically significant differences between EC and UC across the cPRO outcomes over 12 months. The mean change from baseline at each assessment time point for treatment effects (EC vs UC) ranged from -0.19 (95% CI, -0.86 to 0.33; P = .64) for physical function to 0.11 (95% CI, -0.75 to 0.79; P = .87) for fatigue. Zero-inflated negative binomial and logistic regression models showed no significant differences in HCRU outcomes: inpatient and/or observation visits (incidence rate ratio [IRR], 0.90; 95% CI, 0.72-1.12), emergency department and/or urgent care visits (IRR, 0.99; 95% CI, 0.84-1.16), and days of hospital stay (IRR, 1.05; 95% CI, 0.83-1.33).

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, adding a bilingual web-based self-management program to EHR-integrated cPRO did not reduce symptom burden or HCRU compared with cPRO alone. Low engagement with the web-based program highlights the need for strategies to enhance engagement and tailor interventions to those who would benefit most.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03988543.

PMID:40323601 | DOI:10.1001/jamanetworkopen.2025.8353

JAMA Netw Open. 2025 May 1;8(5):e258549. doi: 10.1001/jamanetworkopen.2025.8549.

ABSTRACT

IMPORTANCE: Infants have among the highest rates of emergency department (ED) visits of all age groups. Women with disabilities experience significant social disparities, may experience barriers accessing child primary care, and may seek care in the ED.

OBJECTIVE: To compare ED use among newborns and infants (hereafter infants) of women with or without disabilities, overall and by timing and acuity of the ED visit.

DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study analyzed data for all live-born infants in Ontario, Canada, born to women with or without a disability from April 1, 2008, to March 31, 2021. Data were analyzed March 2023 to October 2024.

EXPOSURE: Maternal physical, sensory, or intellectual or developmental disability or multiple disabilities status was ascertained using diagnostic algorithms applied to health care encounters before delivery.

MAIN OUTCOMES AND MEASURES: The main outcome was any ED visit between an infant’s hospitalization discharge date and their first birthday, and by timing and acuity. Cox proportional hazards regression was used to generate hazard ratios (HRs) for the association between maternal disability and the main outcome, adjusted for sociodemographic characteristics and infant sex and year of birth.

RESULTS: Of 1 596 932 total infants, there were 139 698 (8.7%) born to women with a physical disability, 48 112 (3.0%) to women with a sensory disability, 2547 (0.2%) to women with an intellectual or developmental disability, and 10 312 (0.6%) to women with multiple disabilities. The remaining 1 396 263 infants (87.4%) were born to a woman without a recognized disability. Among women without a disability, 558 965 infants (40.0%) had an ED visit in the first year of life (incidence rate, 1.11 per 1000 person-days). Compared with this referent group, infants born to a woman with a disability of a physical (46.9%; 1.30 visits per 1000 person-days; adjusted HR [AHR], 1.14 [95% CI, 1.13-1.15]), sensory (45.2%; 1.25 visits per 1000 person-days; AHR, 1.09 [95% CI, 1.07-1.10]), or intellectual or developmental (55.4%; 1.55 visits per 1000 person-days; AHR, 1.24 [95% CI, 1.17-1.30]) nature or with multiple disabilities (51.0%; 1.42 visits per 1000 person-days; AHR, 1.18 [95% CI, 1.15-1.22]) were more likely to have an ED visit. Similar patterns were observed for ED visits at fewer than 28 days from delivery, from 28 to 365 days, and for ED visits for high-acuity, moderate-acuity, and low-acuity reasons.

CONCLUSIONS AND RELEVANCE: In this population-based cohort study, infants of women with disabilities were more likely to use the ED, indicating a need for accessible family supports and improved early child primary care access.

PMID:40323599 | DOI:10.1001/jamanetworkopen.2025.8549

JAMA Netw Open. 2025 May 1;8(5):e258558. doi: 10.1001/jamanetworkopen.2025.8558.

ABSTRACT

IMPORTANCE: Evidence of cost savings attributable to indicated and timely care remain rare in psychiatry. Interventions to provide evidence-based psychiatric care to Medicaid patients that lower total costs of care are particularly challenging.

OBJECTIVE: To investigate Medicaid costs and care outcomes associated with use of an outpatient telepsychiatry clinic.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study analyzed Medicaid patients using and not using the services of an outpatient telepsychiatry clinic (Frontier Psychiatry, Billings, Montana) in 2022. Data analysis was performed from June to September 2024.

EXPOSURE: Receipt of care through an outpatient telepsychiatry clinic.

MAIN OUTCOMES AND MEASURES: Differences in Medicaid costs and cost subtypes between telepsychiatry patients and controls were assessed. Quality metrics, including inpatient hospitalizations, hospital readmissions, and admissions from the emergency department, were also compared.

RESULTS: In total, there were 2686 patients using the outpatient telepsychiatry clinic’s services (1665 female [62.0%]; mean [SD] age, 30.55 [14.67] years) and 2686 propensity-matched controls (1665 female [62.0%]; mean [SD] age, 31.37 [15.92] years). Across categories examined, the telepsychiatry patients had care costs per member per month (PMPM) similar to those for propensity-matched control patients ($685.5 [95% CI, $632.9-$738.2] vs $734.0 [95% CI, $645.7-$822.3]; P = .10) over the study period. PMPM costs to Medicaid from the telepsychiatry clinic’s patients were higher for professional services vs control patients ($464.0 [95% CI, $443.4-$484.5] vs $388.4 [95% CI, $368.1-$408.7]; P < .001) but were lower for inpatient hospitalization fees ($201.6 [95% CI, $146.2-$228.7] vs $260.6 [95% CI, $220.2-$341.5]; P = .04). Telepsychiatry clinic patients had a 38.0% lower mean annualized hospitalization rate per 1000 patients than controls (274.3 [95% CI, 237.1-311.6] hospitalizations per 1000 patients vs 442.6 [95% CI, 396.5-488.7] hospitalizations per 1000 patients; P < .001) and a 17.9% lower rate of admissions from the emergency department (patients vs controls, 299.7 admissions [47.7%] vs 519.0 admissions [58.1%]).

CONCLUSIONS AND RELEVANCE: In this cross-sectional study of 5372 patients, use of an outpatient telepsychiatry clinic’s services was associated with decreases in inpatient hospitalization rates and lower rates of admissions from the emergency department, with similar costs to Medicaid. These findings suggest that outpatient telepsychiatry care could play an important role in reducing hospital admissions among patients enrolled in Medicaid.

PMID:40323598 | DOI:10.1001/jamanetworkopen.2025.8558

JAMA Pediatr. 2025 May 5. doi: 10.1001/jamapediatrics.2025.0682. Online ahead of print.

ABSTRACT

IMPORTANCE: Parental technology use in a child’s presence (hereafter, PTU), often referred to as technoference, is a growing concern in family dynamics, and no studies have quantitatively synthesized associations with children’s health and development.

OBJECTIVE: To systematically review and synthesize literature on associations between PTU in their child’s presence and motor development, cognitive development, psychosocial health, physical activity, screen time, and sleep in early childhood.

DATA SOURCES: Peer-reviewed studies from MEDLINE, CINAHL, SPORTDiscus, PsycINFO, PsycArticles, Web of Science, Scopus, and ProQuest published from inception to July 2024.

STUDY SELECTION: A total of 6212 studies were initially identified. Studies were included if they examined associations between PTU in the presence of their apparently healthy children (birth to age 4.9 years) and motor development, cognitive development, psychosocial health, physical activity, screen time, or sleep.

DATA EXTRACTION AND SYNTHESIS: PRISMA guidelines were followed. Random-effect models were conducted to determine the pooled estimates of the associations and moderating effects of the type of exposure (distraction/interruption). The risk of bias was assessed using the JBI critical appraisal tools.

MAIN OUTCOMES AND MEASURES: Association between PTU in the child’s presence and motor development, cognitive development, psychosocial health, physical activity, screen time, and sleep.

RESULTS: Twenty-one studies involving 14 900 participants from 10 countries were included in the meta-analysis. Significant associations were found between parental technology use in the child’s presence and cognition (r = -0.14; 95% CI, -0.23 to -0.04), internalizing behavior and emotions (r = 0.13; 95% CI, 0.08 to 0.19), externalizing behavior (r = 0.15; 95% CI, 0.09 to 0.21), prosocial behavior (r = -0.08; 95% CI, -0.13 to -0.02), attachment (r = -0.10; 95% CI, -0.19 to -0.01), and screen time (r = 0.23; 95% CI, 0.13 to 0.32). No moderating effects of the type of PTU exposure on any associations were found. No study examined motor development, physical activity, or sleep.

CONCLUSIONS AND RELEVANCE: Parents’ use of technology in their child’s presence was negatively associated with cognitive and psychosocial outcomes and screen time among young children, although the effect sizes were small. Further research focusing on potential impacts on physical activity, sleep, and motor skills is needed. Understanding these associations is crucial for informing research and guidelines aimed at minimizing the potential negative effects of this phenomenon on early childhood development.

PMID:40323594 | DOI:10.1001/jamapediatrics.2025.0682

J Craniofac Surg. 2025 May 5. doi: 10.1097/SCS.0000000000011422. Online ahead of print.

ABSTRACT

PURPOSE: Temporal mandibular joint (TMJ) space volume is pivotal in upholding optimal joint function and occlusal stability. Mandibular setback surgery can impact TMJ space volume due to condylar positioning adjustments. This study aims to investigate the changes in TMJ space volume following mandibular setback surgery with intended manual condylar positioning.

METHODS: This is a retrospective study of 20 patients of class III (skeletal), who underwent Le Fort I osteotomy and BSSO surgery at the OMFS Department of PNUDH between 2015 and 2022 by one surgeon. CBCT scans were obtained preoperatively (T0) and at specified postoperative time points (T1) and (T2). The groups were categorized into group A (Total space volume), group B (non-asymmetric), and group C (asymmetric). TMJ space volume measurements were taken using CBCT imaging software. Each slice of the TMJ space was drawn manually using specialized software. The measured areas in each slice were added to determine the TMJ volumes, and the statistical analysis was done.

RESULTS: Preliminary findings from this study indicate that there was a highly significant difference in TMJ space volume between group A, group B, and group C at T0, T1, and T2 following surgery. However, there were no significant differences within the groups, which means that the intended manual condylar positioning gives stability to the TMJ joint space.

CONCLUSIONS: This study suggests that mandibular setback surgery with intended manual condylar positioning can lead to transient changes in TMJ space volume, with subsequent recovery and adaptation.

PMID:40323583 | DOI:10.1097/SCS.0000000000011422

Eur J Epidemiol. 2025 May 5. doi: 10.1007/s10654-025-01235-8. Online ahead of print.

ABSTRACT

In multi-analyst studies, several analysts use the same data to independently investigate identical research questions. Multi-analyst studies have been conducted mainly in psychology, social sciences, and neuroscience, but rarely in epidemiology. Sixteen analyst groups (24 researchers) with backgrounds mainly in statistics, mathematics, and epidemiology were asked to independently perform an analysis on the influence of marital status (never married versus cohabiting married) on cardiovascular outcomes. They were asked to use data from the Survey of Health, Ageing and Retirement in Europe (SHARE), a panel study of 140,000 persons aged 50 years and above from 28 European countries and Israel, and to provide an effect estimate, a comment on their results, and the full syntax of their analyses. In additional analyses beyond the multi-analyst approach, one group selected an exemplary regression model and varied definitions of exposure and outcome and the confounder adjustment set. Each analysis was unique. The size of the 16 datasets used for the analyses ranged from 15,592 to 336,914 observations. The effect estimates (odds ratios, hazard ratios, or relative risks) ranged from 0.72 to 1.02 (reference: cohabiting married) in strictly or partly cross-sectional analyses and from 0.95 to 1.31 in strictly longitudinal analyses. The choice of regression models, adjustment sets for confounding, and variations in the precise definition of exposure and outcome, all had only small effects on the effect estimates. The range of results was mainly due to differences from cross-sectional versus longitudinal analyses rather than to single analytical decisions each of which had less influence.

PMID:40323573 | DOI:10.1007/s10654-025-01235-8

Biodegradation. 2025 May 5;36(3):40. doi: 10.1007/s10532-025-10131-7.

ABSTRACT

Heavy metal pollution in urban freshwater, driven by anthropogenic activities, poses significant risks to aquatic ecosystems and human health due to its toxicity and persistence. Recently, urease-producing bacteria have gained attention for their ability to remove heavy metals through microbial-induced carbonate precipitation (MICP). In this study, eight urease-producing bacteria were exposed to individual solutions of zinc (Zn²⁺), cadmium (Cd²⁺), and nickel (Ni²⁺) at concentrations ranging from 0 to 6 mM to assess their resistance. Three strains-Bacillus subtilis HMZC1 (B2), Bacillus sp. HMZCSW (B6), and Comamonas sp. HMZC (B11)-survived at 4 mM and 6 mM, while most others could not tolerate 4 mM. Their urea-degrading ability was tested at different pH levels, identifying an optimal pH of 7 for MICP. Heavy metal carbonate precipitation experiments at 4 mM and 6 mM revealed that all three strains achieved > 93% removal of Zn²⁺, Ni²⁺, and Cd²⁺ within 72 h. Comamonas sp. HMZC exhibited the highest efficiency, achieving > 95% removal of certain heavy metals at 6 mM. Statistical analysis using one-way ANOVA revealed significant differences (p < 0.05) in heavy metal removal efficiencies among the strains for certain treatment conditions (Cd²⁺ and Zn²⁺ at 4 mM), although not all comparisons reached statistical significance. Scanning Electron Microscopy and X-ray Diffraction confirmed the morphology and composition of the precipitated heavy metal carbonates. Our findings demonstrate that urease-producing bacteria can effectively immobilize multiple heavy metals, highlighting the MICP process as a practical and sustainable biological approach for ecological restoration and wastewater treatment.

PMID:40323541 | DOI:10.1007/s10532-025-10131-7

Int Ophthalmol. 2025 May 5;45(1):170. doi: 10.1007/s10792-025-03553-y.

ABSTRACT

PURPOSE: We aimed to compare corneal thickness maps and ocular surface parameters with anterior segment optical coherence tomography (AS-OCT) between severe obstructive sleep apnea syndrome (OSAS) patients and healthy controls.

METHODS: The study included patients with severe OSAS and healthy subjects. Ocular surface parameters (Schirmer, Tear break-up time (TBUT)), Oxford corneal staining score(OCSS), and Ocular surface disease index (OSDI) score were evaluated, and corneal thickness maps (total and epithelial) were obtained by AS-OCT in all participants.

RESULTS: The mean ages of the control (n:30) and patient (n:30) groups were 44.80 ± 6.5 and 48.3 ± 8.9 years, respectively (p:0.09). The mean Apnea hypopnea index (AHI) in the patient group was 64.53 ± 21.25, mean body mass index (BMI) was 31.33 ± 3.66. TBUT, Schirmer tests, OCSS and OSDI score were statistically significantly different between the groups (p < 0.001, p:0.037, p < 0.001, p < 0.001, respectively). There was no significant difference between the groups in the parameters in the corneal thickness maps using OCT.

CONCLUSION: Ocular surface parameters may worsen in OSAS. There were no significant differences among groups in corneal epithelial thickness mapping using AS-OCT. Further research is needed to explore the long-term effects of the disease on corneal morphology.

PMID:40323536 | DOI:10.1007/s10792-025-03553-y

Inflammopharmacology. 2025 May 5. doi: 10.1007/s10787-025-01770-6. Online ahead of print.

ABSTRACT

This study determined the phytochemical profile and in vivo anti-arthritic potential and mechanistic effects of MeOH extract of Rhamnus prinoides. The liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) were used in the phytochemical analysis of the extract. In the anti-arthritic assay, the rats were assigned into arthritic control, non-arthritic control, methotrexate control, and three extract-treated [100, 200, and 300 mg/kg body weight (bw)] groups. Complete Freund’s adjuvant was used to induce polyarthritis. The treatments were orally administered from day 8 post-induction of polyarthritis. The experimental animals were euthanized and blood was drawn for hematological parameter analysis on day 29. The ankle joint tissue and liver were detached and utilized in gene expression using RT-qPCR and standard antioxidant assays, respectively. One-factorial ANOVA and Tukey’s multiple comparisons were used to compute for statistical differences of the raw data. The LC-MS analysis identified phytochemicals of flavonoids, anthraquinones, lignans, and coumarins classes. Fatty acid methyl ester, benzofuran, and terpene were also detected using GC-MS. The extract significantly reduced ankle joint edema, reduced body weight loss and arthritis scores, improved elevated spleen and thymus indices, attenuated aberrant hematological parameters, lowered malonaldehyde levels, and enhanced enzymatic antioxidant activities in rats induced with polyarthritis (p < 0.05). The extract also significantly upregulated expression of I-κBα, IL-4, and IL-10 genes, as well as downregulated expression of STAT-3, NF-κB, RANKL, COX-2, TNF-α, and IL-6 genes in rats induced with polyarthritis (p < 0.05). The extract possesses phytochemicals with anti-arthritic potential and can be used as a potential lead in developing novel anti-arthritic agents.

PMID:40323528 | DOI:10.1007/s10787-025-01770-6